Clinical Review


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Here are recommendations, and cautions, when you are considering a patient’s request for preimplantation genetic diagnosis or screening



The author reports no financial relationships relevant to this article.

Population-based screening for carriers of genetic diseases and advances in neonatal and pediatric genetic testing have resulted in more and more couples identified as at-risk for inherited disorders. Increasingly, women in these couples ask their ObGyn about their options for future pregnancies.

For some women, genetic testing of a pregnancy as early as possible—even before implantation—is desirable. In vitro fertilization affords such direct access to the genetic material of either gametes before fertilization (i.e., polar-body biopsy) or blastomeres once fertilization has occurred (blastomere biopsy). Complex genetic analysis of these single cells is now possible. Because polar-body biopsy is restricted to testing for maternal disease, blastomere biopsy has gained favor as the method of choice for genetic testing of preimplantation pregnancies.

The duality of genetic testing

Regardless of what genetic material is tested, preimplantation genetic testing encompasses two distinct categories: preimplantation genetic diagnosis, or PGD, and preimplantation genetic screening, or PGS.

What is PGD?

Here, testing is confined to women at risk of an offspring with an identified genetic abnormality. These women, or their partner, typically carry a gene mutation that, alone or in combination with another mutation in the same gene, would result in an identifiable outcome in their child (for example, autosomal-recessive, autosomal-dominant, and X-linked disorders).

PGD, by definition, also includes testing of women, or their partner, who possess a balanced chromosome rearrangement (translocation, inversion). Offspring of carriers of balanced chromosome rearrangements are at increased risk of particular genetic abnormalities, as a result of unbalanced segregation of chromosomes involved in their rearrangement.

How does PGS differ from PGD?

Screening, in contrast, focuses analysis on offspring of women who are theoretically at increased risk of a genetic abnormality based on their age or reproductive history, not on their genetic makeup. PGS looks specifically for chromosomal content, and is based on the premise that decreasing the rate of aneuploidy among the conceptions of women 1) of advanced maternal age, 2) who experience habitual miscarriage, or 3) who have failed multiple cycles of in vitro fertilization (IVF) would increase the rate of implantation and, ultimately, the live birth rate.

The articles below, beginning with a committee opinion from the American Society for Reproductive Medicine (ASRM), address the following:

  • evidence in support of PGD for genetic disease
  • caution about using PGS, in its current format, for aneuploidy screening.

PGD can reduce the risk of a child with a specific genetic abnormality carried by one or both parents

Practice Committee of the Society for Assisted Reproductive Technology; Practice Committee of the American Society for Reproductive Medicine. Preimplantation genetic testing: a Practice Committee opinion. Fertil Steril. 2007;88:1497–1504.

A gene mutation carried by one or both parents can increase the risk that their offspring will be affected with an inherited condition. Common examples include autosomal-recessive disorders such as cystic fibrosis; autosomal-dominant disorders such as neurofibromatosis; and X-linked disorders such as hemophilia A.

Recently, human leukocyte antigens (HLA) have been assessed in conjunction with testing for specific genetic diseases, such as Fanconi anemia. In these settings, the intent is to recognize not only the blastomeres that are free of Fanconi anemia, but also those that are potential HLA matches and, therefore, potential donors for an (older) affected sibling.

PGD has been extended to women, or their partner, who possess a gene mutation that places them at increased risk of cancer (such as BRCA-1) and who wish to avoid transmitting that risk-conferring gene to their offspring.

For these diseases, and for many others, knowledge of the specific genetic mutation enables similar molecular testing to be accomplished on a single cell, such as a blastomere.

Technical concerns of testing must be part
of the physician–patient discussion

Typically, PGD analysis is initiated by polymerase chain reaction (PCR) of DNA content extracted from the single cell. This is followed by application of mutation-appropriate molecular technology. Given 1) the short time in which these PGD results are needed (often, 24 to 48 hours) and 2) the limited amount of genetic material available for analysis, technical restraints on testing are recognized:


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